Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats

Essential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, stor...

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Main Authors: Jereme G. Spiers, Li Si Tan, Stephen T. Anderson, Andrew F. Hill, Nickolas A. Lavidis, Hsiao-Jou Cortina Chen
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/1/85
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author Jereme G. Spiers
Li Si Tan
Stephen T. Anderson
Andrew F. Hill
Nickolas A. Lavidis
Hsiao-Jou Cortina Chen
author_facet Jereme G. Spiers
Li Si Tan
Stephen T. Anderson
Andrew F. Hill
Nickolas A. Lavidis
Hsiao-Jou Cortina Chen
author_sort Jereme G. Spiers
collection DOAJ
description Essential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, storage, and secretion. Some metal ions can be transformed by processes including reduction/oxidation (redox) reactions, and correspondingly, the breakdown of metal ion homeostasis can lead to formation of reactive oxygen and nitrogen species. We have previously demonstrated rapid biochemical responses to stress involving alterations in the redox state to generate free radicals and the resultant oxidative stress. However, the effects of stress on redox-active metals including iron and copper and redox-inert zinc have not been well characterised. Therefore, this study aims to examine the changes in these essential metals following exposure to short-term repeated stress, and to further elucidate the alterations in metal homeostasis through expression analysis of different metal transporters. Outbred male Wistar rats were exposed to unrestrained (control), 1 day, or 3 days of 6 h restraint stress (<i>n</i> = 8 per group). After the respective stress treatment, blood and liver samples were collected for the analysis of biometal concentrations and relative gene expression of metal transporter and binding proteins. Exposure to repeated restraint stress was highly effective in causing hepatic redox imbalance. Stress was also shown to induce hepatic metal redistribution, while modulating the mRNA levels of key metal transporters. Overall, this study is the first to characterise the gene expression profile of metal homeostasis following stress and provide insight into the changes occurring prior to the onset of chronic stress conditions.
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spelling doaj.art-640d369ecb9f4283930fa32ccf55f4892023-11-23T12:47:04ZengMDPI AGAntioxidants2076-39212021-12-011118510.3390/antiox11010085Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in RatsJereme G. Spiers0Li Si Tan1Stephen T. Anderson2Andrew F. Hill3Nickolas A. Lavidis4Hsiao-Jou Cortina Chen5Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083, AustraliaSchool of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane 4072, AustraliaSchool of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane 4072, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora 3083, AustraliaSchool of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane 4072, AustraliaSchool of Biomedical Sciences, The University of Queensland, St. Lucia, Brisbane 4072, AustraliaEssential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, storage, and secretion. Some metal ions can be transformed by processes including reduction/oxidation (redox) reactions, and correspondingly, the breakdown of metal ion homeostasis can lead to formation of reactive oxygen and nitrogen species. We have previously demonstrated rapid biochemical responses to stress involving alterations in the redox state to generate free radicals and the resultant oxidative stress. However, the effects of stress on redox-active metals including iron and copper and redox-inert zinc have not been well characterised. Therefore, this study aims to examine the changes in these essential metals following exposure to short-term repeated stress, and to further elucidate the alterations in metal homeostasis through expression analysis of different metal transporters. Outbred male Wistar rats were exposed to unrestrained (control), 1 day, or 3 days of 6 h restraint stress (<i>n</i> = 8 per group). After the respective stress treatment, blood and liver samples were collected for the analysis of biometal concentrations and relative gene expression of metal transporter and binding proteins. Exposure to repeated restraint stress was highly effective in causing hepatic redox imbalance. Stress was also shown to induce hepatic metal redistribution, while modulating the mRNA levels of key metal transporters. Overall, this study is the first to characterise the gene expression profile of metal homeostasis following stress and provide insight into the changes occurring prior to the onset of chronic stress conditions.https://www.mdpi.com/2076-3921/11/1/85copperessential metalsironliverratredox
spellingShingle Jereme G. Spiers
Li Si Tan
Stephen T. Anderson
Andrew F. Hill
Nickolas A. Lavidis
Hsiao-Jou Cortina Chen
Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
Antioxidants
copper
essential metals
iron
liver
rat
redox
title Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
title_full Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
title_fullStr Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
title_full_unstemmed Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
title_short Hepatic Homeostasis of Metal Ions Following Acute Repeated Stress Exposure in Rats
title_sort hepatic homeostasis of metal ions following acute repeated stress exposure in rats
topic copper
essential metals
iron
liver
rat
redox
url https://www.mdpi.com/2076-3921/11/1/85
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AT andrewfhill hepatichomeostasisofmetalionsfollowingacuterepeatedstressexposureinrats
AT nickolasalavidis hepatichomeostasisofmetalionsfollowingacuterepeatedstressexposureinrats
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